JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib.
Haematologica
PUBLISHED: 05-16-2014
Show Abstract
Hide Abstract
The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier:00055874).
Related JoVE Video
Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma.
J. Clin. Oncol.
PUBLISHED: 02-03-2014
Show Abstract
Hide Abstract
R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is standard care for aggressive B-cell lymphoma. A prospective trial was conducted to investigate the role of additive radiotherapy (RT) to bulky and extralymphatic disease.
Related JoVE Video
Severe conjunctivitis due to multidrug-resistant Neisseria gonorrhoeae and adenovirus 53 coinfection in a traveler returning from Thailand.
J Travel Med
PUBLISHED: 07-11-2013
Show Abstract
Hide Abstract
A male traveler returning from Thailand with severe bilateral conjunctivitis was tested for causative pathogens by culture and polymerase chain reaction in late 2010. The culturally grown Neisseria gonorrhoeae strain was resistant against penicillin, ciprofloxacin, and tetracycline. The patient was also found to have an eye infection with the unusual and likely recombinant adenovirus type 53. Besides multidrug-resistant gonococcal strains the unusual adenovirus strain is found circulating in Asia and both pathogens may be a risk for travelers.
Related JoVE Video
Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria.
Br. J. Haematol.
PUBLISHED: 01-17-2013
Show Abstract
Hide Abstract
Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.
Related JoVE Video
Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.
Blood
PUBLISHED: 10-28-2011
Show Abstract
Hide Abstract
The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.
Related JoVE Video
Complete sequence of a cryptic virus from hemp (Cannabis sativa).
Arch. Virol.
PUBLISHED: 08-09-2011
Show Abstract
Hide Abstract
Hemp (Cannabis sativa) was found to be a useful propagation host for hop latent virus, a carlavirus. However, when virus preparations were analysed by electron microscopy, along with the expected filamentous particles, spherical particles with a diameter of around 34 nm were found. RNA from virus preparations was purified, and cDNA was prepared and cloned. Sequence information was used to search databases, and the greatest similarity was found with Primula malacoides virus 1, a putative new member of the genus Partitivirus. The full sequences of RNA 1 and RNA 2 of this new hemp cryptic virus were obtained.
Related JoVE Video
The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells.
EMBO J.
PUBLISHED: 01-11-2011
Show Abstract
Hide Abstract
Notch signalling is important for development and tissue homeostasis and activated in many human cancers. Nevertheless, mutations in Notch pathway components are rare in solid tumours. ZEB1 is an activator of an epithelial-mesenchymal transition (EMT) and has crucial roles in tumour progression towards metastasis. ZEB1 and miR-200 family members repress expression of each other in a reciprocal feedback loop. Since miR-200 members target stem cell factors, ZEB1 indirectly induces stemness maintenance and associated drug resistance. Here, we link ZEB1 and its cancer promoting properties to Notch activation. We show that miR-200 members target Notch pathway components, such as Jagged1 (Jag1) and the mastermind-like coactivators Maml2 and Maml3, thereby mediating enhanced Notch activation by ZEB1. We further detected a coordinated upregulation of Jag1 and ZEB1, associated with reduced miR-200 expression in two aggressive types of human cancer, pancreatic adenocarcinoma and basal type of breast cancer. These findings explain increased Notch signalling in some types of cancers, where mutations in Notch pathway genes are rare. Moreover, they indicate an additional way how ZEB1 exerts its tumour progressing functions.
Related JoVE Video
Complete nucleotide sequence and evolutionary analysis of a gorilla foamy virus.
J. Gen. Virol.
PUBLISHED: 11-24-2010
Show Abstract
Hide Abstract
To shed light on primate foamy virus (FV) evolution, we determined the complete nucleotide sequence of the gorilla simian foamy virus (SFVgor). Starting from a conserved region in the integrase (IN) domain of the pol gene we cloned the viral genome to the 5 and 3 LTR into plasmid vectors and elucidated its nucleotide sequence. The sequences of both LTRs were determined by nucleotide sequencing of separate PCR products from the primer-binding site or the bel region and LTRs. All protein motifs conserved among the primate FV were identified in SFVgor. Using phylogenetic analysis of the Gag, Pol and Env amino acid sequences, we demonstrate that SFVgor consistently clusters in accordance with a scenario of virus-host co-divergence.
Related JoVE Video
Reduced treatment intensity in patients with early-stage Hodgkins lymphoma.
N. Engl. J. Med.
PUBLISHED: 09-08-2010
Show Abstract
Hide Abstract
Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkins lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels.
Related JoVE Video
Desmoplakin and KIF20B as target antigens in patients with paroxysmal nocturnal haemoglobinuria.
Br. J. Haematol.
PUBLISHED: 08-31-2010
Show Abstract
Hide Abstract
At least two hypotheses have been proposed to explain the mechanism of clonal expansion of mutant cells in paroxysmal nocturnal haemoglobinuria (PNH). One hypothesis assumes an immune escape mechanism and another proposes an intrinsic second mutational event within clonal cells. We hypothesised that autoantibodies detected in PNH patients could identify antigens that might play a role in the pathophysiology of this disease and screened a human fetal liver cDNA library for serological reactivity against haematopoietic stem/progenitor cells antigens using the SEREX approach. Two antigens were identified that are constitutively expressed in CD34(+) cells. Three and four of 10 PNH patients showed antibody responses against kinesin family member 20B (KIF20B) (previously termed M-phase phosphoprotein 1, MPP1) and desmoplakin (DSP) respectively. We also found an antibody response in one of 20 healthy volunteers against desmoplakin, yet at a much lower titre than in PNH patients. No response to KIF20B or desmoplakin was detected in five patients with aplastic anaemia without a glycosyl phosphatidyl inositol -deficient clone. We conclude that KIF20B and desmoplakin have been shown to be the first known auto-antigens to be recognised by the immune system of patients with PNH. The analysis of the mechanisms underlying the autoimmune response might contribute to our understanding of the clonal expansion in PNH.
Related JoVE Video
High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors.
BMC Infect. Dis.
PUBLISHED: 07-20-2010
Show Abstract
Hide Abstract
DNA of the polyomaviruses WU (WUPyV) and KI (KIPyV) and of human bocavirus (HBoV) has been detected with varying frequency in respiratory tract samples of children. However, only little is known about the humoral immune response against these viruses. Our aim was to establish virus-specific serological assays and to determine the prevalence of immunoglobulin G (IgG) against these three viruses in the general population.
Related JoVE Video
Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.
Blood
PUBLISHED: 07-01-2010
Show Abstract
Hide Abstract
The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.
Related JoVE Video
Characterization of the multiple resistance traits of somatic hybrids between Solanum cardiophyllum Lindl. and two commercial potato cultivars.
Plant Cell Rep.
PUBLISHED: 04-26-2010
Show Abstract
Hide Abstract
Interspecific somatic hybrids between commercial cultivars of potato Solanum tuberosum L. Agave and Delikat and the wild diploid species Solanum cardiophyllum Lindl. (cph) were produced by protoplast electrofusion. The hybrid nature of the regenerated plants was confirmed by flow cytometry, simple sequence repeat (SSR), amplified fragment length polymorphism (AFLP), microsatellite-anchored fragment length polymorphism (MFLP) markers and morphological analysis. Somatic hybrids were assessed for their resistance to Colorado potato beetle (CPB) using a laboratory bioassay, to Potato virus Y (PVY) by mechanical inoculation and field trials, and foliage blight in a greenhouse and by field trials. Twenty-four and 26 somatic hybrids of cph + cv. Agave or cph + cv. Delikat, respectively, showed no symptoms of infection with PVY, of which 3 and 12, respectively, were also resistant to foliage blight. One hybrid of cph + Agave performed best in CPB and PVY resistance tests. Of the somatic hybrids that were evaluated for their morphology and tuber yield in the field for 3 years, four did not differ significantly in tuber yield from the parental and standard cultivars. Progeny of hybrids was obtained by pollinating them with pollen from a cultivar, selfing or cross-pollination. The results confirm that protoplast electrofusion can be used to transfer the CPB, PVY and late blight resistance of cph into somatic hybrids. These resistant somatic hybrids can be used in pre-breeding studies, molecular characterization and for increasing the genetic diversity available for potato breeding by marker-assisted combinatorial introgression into the potato gene pool.
Related JoVE Video
The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab.
Br. J. Haematol.
PUBLISHED: 02-11-2010
Show Abstract
Hide Abstract
In Paroxysmal nocturnal haemoglobinuria (PNH), pregnancy is associated with increased maternal and foetal complications to such an extent that the condition has been considered relatively contra-indicated in PNH. Eculizumab has revolutionized the treatment of PNH. We evaluate its use in pregnancy to date. We report on seven patients exposed to eculizumab at different stages of pregnancy including the first two patients to receive the drug from conception to delivery. There was no evidence of complement blockade from cord blood samples taken at delivery. Eculizumab appears safe to use in this setting and is likely to prevent many of the complications usually observed.
Related JoVE Video
Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
Blood
PUBLISHED: 10-07-2009
Show Abstract
Hide Abstract
From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 mg/m(2))-based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related (n = 33) or unrelated donors (n = 70). All but 2 patients (2%) showed leukocyte and platelet engraftment after a median of 18 and 22 days, respectively. Acute graft-versus-host disease grade 2 to 4 occurred in 27% and chronic graft-versus-host disease in 43% of the patients. Cumulative incidence of nonrelapse mortality at 1 year was 16% (95% confidence interval, 9%-23%) and significantly lower for patients with a completely matched donor (12% vs 38%; P = .003). The cumulative incidence of relapse at 3 years was 22% (95% confidence interval, 13%-31%) and was influenced by Lille risk profile (low, 14%; intermediate, 22%; and high, 34%; P = .02). The estimated 5-year event-free and overall survival was 51% and 67%, respectively. In a multivariate analysis, age older than 55 years (hazard ratio = 2.70; P = .02) and human leukocyte antigen-mismatched donor (hazard ratio = 3.04; P = .006) remained significant factors for survival. The study was registered at www.clinicaltrials.gov as #NCT 00599547.
Related JoVE Video
Detection of Meningeosis neoplastica by real-time quantitation of telomerase activity.
Clin. Chem. Lab. Med.
PUBLISHED: 09-12-2009
Show Abstract
Hide Abstract
Background: Analysis of cerebrospinal fluid (CSF) to discriminate between benign and malignant conditions is of fundamental importance for the physician and the patient because of the differential therapeutic options and resulting morbidity and mortality. Most human tumours demonstrate increased telomerase activity (TA). Recent technical advances in the detection of TA allow for sensitive and specific detection within 4 h. Thus, the detection of TA is suitable for routine clinical testing.
Related JoVE Video
The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs.
Nat. Cell Biol.
PUBLISHED: 05-06-2009
Show Abstract
Hide Abstract
Invasion and metastasis of carcinomas is promoted by the activation of the embryonic epithelial to mesenchymal transition (EMT) program, which triggers cellular mobility and subsequent dissemination of tumour cells. We recently showed that the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) is a crucial promoter of metastasis and demonstrated that ZEB1 inhibits expression of the microRNA-200 (miR-200) family, whose members are strong inducers of epithelial differentiation. Here, we report that ZEB1 not only promotes tumour cell dissemination, but is also necessary for the tumour-initiating capacity of pancreatic and colorectal cancer cells. We show that ZEB1 represses expression of stemness-inhibiting miR-203 and that candidate targets of miR-200 family members are also stem cell factors, such as Sox2 and Klf4. Moreover, miR-200c, miR-203 and miR-183 cooperate to suppress expression of stem cell factors in cancer cells and mouse embryonic stem (ES) cells, as demonstrated for the polycomb repressor Bmi1. We propose that ZEB1 links EMT-activation and stemness-maintenance by suppressing stemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells. Thus, targeting the ZEB1-miR-200 feedback loop might form the basis of a promising treatment for fatal tumours, such as pancreatic cancer.
Related JoVE Video
Complementation analysis of triple gene block of Potato virus S (PVS) revealed its capability to support systemic infection and aphid transmissibility of recombinant Potato virus X.
Virus Res.
PUBLISHED: 05-06-2009
Show Abstract
Hide Abstract
Triple gene block (TGB) sequences derived from isolates of ordinary Potato virus S (PVS-O) and Chenopodium-systemic (PVS-CS) were analyzed. Although the TGB sequences did not reveal any specific difference within the 7K protein, some specific differences within the 25K and 12K ORFs were found. In order to investigate a possible functional divergence of PVS-O and PVS-CS TGB variants, these genes were propagated in chimeric Potato virus X (PVX). Both PVS TGB variants partly complemented PVX TGB in Nicotiana benthamiana. The recombinant viruses multiplied to lower titer than the wild-type PVX in N. benthamiana showed attenuated symptoms. Whereas the recombinant PVX variants were also propagated systemically in Nicotiana glutinosa, Celosia argentea, Nicotiana occidentalis and chimeric PVX bearing TGB from PVS-O in Solanum lycopersicum, neither were propagated systemically in Chenopodium quinoa nor in Nicotiana tabacum cv. Samsun nn and the PVX-resistant Solanum tuberosum cv. Szignal. The potential for recombinant viruses to be transmitted by the aphid Myzus persicae was investigated. Aphid transmission in the recombinant virus was obtained by replacing PVX TGB by TGB from the PVS-CS isolate. These results show the potential function of Carlavirus TGB in aphid transmissibility and underlines the possible biological risks from certain recombinant virus variants.
Related JoVE Video
Biological and molecular analysis of the pathogenic variant C3 of potato spindle tuber viroid (PSTVd) evolved during adaptation to chamomile (Matricaria chamomilla).
Biol. Chem.
Show Abstract
Hide Abstract
Viroid-caused pathogenesis is a specific process dependent on viroid and host genotype(s), and may involve viroid-specific small RNAs (vsRNAs). We describe a new PSTVd variant C3, evolved through sequence adaptation to the host chamomile (Matricaria chamomilla) after biolistic inoculation with PSTVd-KF440-2, which causes extraordinary strong (lethal) symptoms. The deletion of a single adenine A in the oligoA stretch of the pathogenicity (P) domain appears characteristic of PSTVd-C3. The pathogenicity and the vsRNA pool of PSTVd-C3 were compared to those of lethal variant PSTVd-AS1, from which PSTVd-C3 differs by five mutations located in the P domain. Both lethal viroid variants showed higher stability and lower variation in analyzed vsRNA pools than the mild PSTVd-QFA. PSTVd-C3 and -AS1 caused similar symptoms on chamomile, tomato, and Nicotiana benthamiana, and exhibited similar but species-specific distributions of selected vsRNAs as quantified using TaqMan probes. Both lethal PSTVd variants block biosynthesis of lignin in roots of cultured chamomile and tomato. Four expression markers (TCP3, CIPK, VSF-1, and VPE) were selected from a tomato EST library to quantify their expression upon viroid infection; these markers were strongly downregulated in tomato leaf blades infected by PSTVd-C3- and -AS1 but not by PSTVd-QFA.
Related JoVE Video
Activation of canonical WNT/?-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition.
Cancer Lett.
Show Abstract
Hide Abstract
Here we show that activation of the canonical WNT/?-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for ?-catenin in the infiltrating edge of tumor compared to central tumor parenchyma. These findings suggest that canonical WNT/?-catenin pathway is a critical regulator of GBM invasion and may represent a potential therapeutic target.
Related JoVE Video
Analysis of complete genomes of isolates of the Wheat dwarf virus from new geographical locations and descriptions of their defective forms.
Virus Genes
Show Abstract
Hide Abstract
Recently, the importance of the Geminiviruses infecting cereal crops has been appreciated, and they are now being studied in detail. Barley and wheat strains of Wheat dwarf virus are recorded in most European countries. Information on complete sequences of isolates from the United Kingdom, Spain, and Austria are reported here for the first time. Analysis revealed that their sequences are very stable. Recombination between strains was recorded only for the barley strain. We identified several defective forms of the barley strain from barley and wheat, which do not influence symptom expression. Sequences of barley isolates infecting wheat were obtained that did not differ from the isolates from barley. Based on specific features of the SIR of the barley strains, it is suggested that they are assigned to one of the two proposed new clusters, A1 or A2.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.